Secretory microRNAs as biomarkers of cancer

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression predominantly by inhibiting transcription and/or promoting degradation of target mRNAs also in addition to being involved in non-canonical mechanisms regulating transcription, translation and cell signaling processes. Extracellular secretory miRNAs, either in complex with specific proteins or encapsulated in microvesicles called exosomes, are transported between cells as means of intercellular communication. Secretory miRNAs in circulation remain functional after delivery to recipient cells, regulating target genes and their corresponding signaling pathways. Cancer cell secreted miRNA-mediated intercellular communication affects physiological processes associated with the disease, such as, angiogenesis, metabolic reprogramming, immune modulation, metastasis, and chemo-resistance. Given the stability of miRNAs in body fluids and their well-documented roles in deregulating cancer-relevant genetic pathways, there is considerable interest in developing secretory miRNAs as liquid biopsy biomarkers for detection, diagnosis and prognostication of cancer. In this review, we discuss salient features of miRNA biogenesis, secretion and function in cancer as well as the current state of secretory miRNA isolation and profiling methods. Furthermore, we discuss the challenges and opportunities of secretory miRNA biomarker assay development, which need to be addressed for clinical applications.